Urge urinary incontinence, the abnormal spontaneous contraction of the bladder detrusor muscle leading to a sense of urinary urgency and involuntary urine loss is currently a condition where there exists an unmet medical need (Primeau et al., Current Pharmaceutical Design, 1995, 1, 391). The current treatments for this condition are the use of anticholinergics and anticholinergic/antispasmodics which have the limitations of CNS related side effects and low efficacy which leads to poor patient compliance. Hyperpolarization of bladder smooth muscle leading to the relaxation of detrusor muscle contractions may represent a novel therapeutic approach to urge urinary incontinence.
Few examples of simple 4,5-diantinopyrazoles have appeared in the chemical or patent literature. Moderhack describes the synthesis of several 4,5-diaminopyrazoles as intermediates towards the synthesis of 1,2,4-triazoles (Liebigs Ann. 1996, 777-9). Lewis et al. describe the synthesis of various 4,5-diaminopyrazoles (J. Heterocyclic Chem. 1983, 20, 1501-3).
The synthetic procedure used to make the diaminopyrazoles reported in this invention record is based on the procedure of Vicentini et al. (Tetrahedron 1990, 46, 5777-88 and Tetrahedron Lett. 1988, 29, 6171-2) which outlines the synthesis of 4-nitroso-5-aminopyrazoles as intermediates in the synthesis of imidazole[4,5-c]pyrazoles.